中文摘要：

目的探讨泛素样蛋白蛋白酶体系统对单耐异烟肼结核分枝杆菌耐药性的影响及其机制。方法采用刃天青显色法,比较单耐异烟肼结核分枝杆菌（对照组）与4种基因（Pup、Dop、PafA、Mpa基因）分别过表达和缺失单耐异烟肼结核分枝杆菌菌株异烟肼最低抑菌浓度（minimum inhibitory concentration,MIC）值的差异;比较加入改变细胞壁通透性试剂后,单耐异烟肼结核分枝杆菌（对照组）与4种基因分别过表达和缺失单耐异烟肼结核分枝杆菌菌株异烟肼MIC差值间的差异。结果 （1）与单耐异烟肼结核分枝杆菌相比,异烟肼的MIC值过表达PafA基因株增加1.03μg/ml,过表达Dop、Mpa基因株分别降低1.03μg/ml、0.68μg/ml,差异均无统计学意义（F=1.898,P〉0.05）;过表达Pup基因株异烟肼的MIC值增加8μg/ml,差异有统计学意义（t=2.185,P〈0.05）;缺失Pup、Dop、PafA、Mpa基因株异烟肼的MIC值分别降低4.82、4.98、4.99、4.9μg/ml,差异均有统计学意义（F=35.809,P〈0.05）。（2）与加入改变细胞壁通透性试剂后单耐异烟肼结核分枝杆菌相比,异烟肼的MIC差值过表达Pup基因株增加7.78μg/ml,差异有统计学意义（t=2.173,P〈0.05）;缺失Pup、Dop、PafA、Mpa基因株分别降低4.58、4.73、4.75、4.68μg/ml,差异均有统计学意义（F=33.598,P〈0.05）;过表达Dop、Mpa基因株分别降低1μg/ml和0.7μg/ml,过表达PafA基因株增加0.97μg/ml,差异均无统计学意义（F=1.935,P〉0.05）。结论结核分枝杆菌泛素样蛋白蛋白酶体系统可能通过调控单耐异烟肼结核分枝杆菌细胞壁的通透性影响其耐药性。

英文摘要：

Objective To examine the effects of and mechanism by which the ubiquitin-like protein-proteasome system confers drug resistance to isoniazid-monoresistant Mycobacteriurn tuberculosis （INH MTB）. Methods A resazurin re- duction assay was used to compare differences in the minimum inhibitory concentration （MIC） of isoniazid for INH-MTB （the control group） and for INH-MTB over-expressing one of four genes （Pup, Dop, PafA, and Mpa） or with deletion of one of those four genes （△Pup, △Dop, △PafA, and △Mpa）. An agent was administered to change cell wall permeabili- ty, and differences in the MIC of isoniazid were compared between INH-MTB （the control group） and INH-MTB over- expressing a given gene or with a given gene deleted. Results （1） The MIC of isoniazid was 1.03 μg/ml higher for INH-MTB over-expressing PafA than for the control INH-MTB. The MIC of isoniazid was 1.03 μg/ml lower for INH-MTB over expressing Dop and 0. 68 μg/ml lower for INH-MTB over-expressing Mpa than for the control INH--MTB. The MIC of isoniazid did not differ significantly for INH-MTB over-expressing one of those 3 genes （F 1. 898, P〈 0.05）. The MIC of isoniazid was 8 btg/ml higher for INH-MTB over expressing Pup than for the control INH MTB, and the MIC of isoniazid differed significantly for INH-MTB over-expressing that gene （t=2. 185, P〈0.05）. The MIC of i- soniazid was 4.82 μg/ml lower for INH-MTB with Pup deleted than that for the control INH MTB, 4. 98 μg/ml lower for INH-MTB with Dop deleted, 4.99 μg/ml lower for INH-MTB with PafA deleted, and 4.9 μg/ml lower for INH MTB with Mpa deleted. The MIC of isoniazid differed significantly for INH MTB with one of those genes deleted （F= 35. 809, P〈0.05）. （2） After an agent was used to change cell wall permeability, the MIC of isoniazid was 7.78μg/ml higher for INH-MTB over-expressing Pup than for the control INH-MTB, and the MIC of isoniazid differed significantly for INH-MTB over-expressing that gene （t =2. 173, P〈0.05）. The